Is Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) effective for treating Hepatitis B (HBV)?

Symtuza Is Not Effective for Treating Hepatitis B Alone, But Components Are Useful in HIV/HBV Coinfection

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) should not be used specifically for treating Hepatitis B infection alone, but its components emtricitabine and tenofovir alafenamide are effective against HBV in the context of HIV/HBV coinfection.

Components of Symtuza and Their Activity Against HBV

Symtuza contains four medications:

• Darunavir (protease inhibitor) - no activity against HBV
• Cobicistat (pharmacokinetic enhancer) - no activity against HBV
• Emtricitabine - active against HBV
• Tenofovir alafenamide (TAF) - active against HBV

Only two of these components (emtricitabine and tenofovir alafenamide) have anti-HBV activity. These two medications are nucleos(t)ide analogs that inhibit HBV DNA polymerase 1.

Appropriate Use of Symtuza Components in HBV Treatment

For HBV Monoinfection:

For patients with chronic HBV infection without HIV, Symtuza is not appropriate. Instead:

• First-line treatments for chronic HBV include entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) as monotherapy 1
• Tenofovir alafenamide (25mg) is FDA-approved specifically for HBV treatment with a high barrier to resistance 1, 2
• Emtricitabine alone is not recommended for HBV due to high resistance rates 1

For HIV/HBV Coinfection:

For patients coinfected with HIV and HBV, the components in Symtuza that are active against HBV (emtricitabine and tenofovir alafenamide) are actually recommended as part of HIV therapy:

• A fully suppressive antiretroviral regimen that includes tenofovir (either TAF or TDF) plus emtricitabine or lamivudine is recommended for patients with HIV/HBV coinfection 3
• This approach treats both viruses simultaneously and prevents development of resistance 3
• The combination of tenofovir plus emtricitabine may reduce the development of tenofovir-resistant HBV 1, 3

Important Warnings and Considerations

1. Risk of Severe Hepatitis Flares:

   • Severe acute exacerbations of hepatitis B have been reported in patients who discontinue anti-HBV therapy 4
   • Hepatic function should be monitored closely if emtricitabine or tenofovir is discontinued 4

2. Resistance Concerns:

   • Using only one anti-HBV agent (like emtricitabine alone) can lead to high rates of resistance (up to 90% at 4 years in coinfected patients) 3
   • Tenofovir has a high genetic barrier to resistance with no documented resistance after up to 8 years of treatment 1

3. Monitoring Requirements:

   • Regular assessment of liver function and viral load monitoring is essential 3
   • For patients with HBV/HIV coinfection, both HIV RNA and HBV DNA levels should be monitored 3

Treatment Algorithm for HBV

1. For HBV monoinfection:

   • Use entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide monotherapy 1
   • Do NOT use Symtuza or its individual components in isolation

2. For HIV/HBV coinfection:

   • Use a fully suppressive HIV regimen that includes tenofovir (TAF or TDF) plus emtricitabine 3
   • A regimen like bictegravir-TAF-emtricitabine would be preferred over Symtuza for most patients with HIV/HBV coinfection 3, 5
   • The ALLIANCE trial demonstrated superior HBV DNA suppression with bictegravir, emtricitabine, and tenofovir alafenamide compared to dolutegravir, emtricitabine, and tenofovir disoproxil fumarate in coinfected patients 5

Conclusion

While Symtuza itself is not indicated for treating HBV infection alone, two of its components (emtricitabine and tenofovir alafenamide) are effective against HBV when used appropriately in combination therapy, particularly in the context of HIV/HBV coinfection. For HBV monoinfection, other approved therapies should be used instead.